Inhibition of drug-metabolizing enzymes in the rat after bacillus calmette-guérin treatment

Drug-metabolizing enzyme activities and protein content of hepatic microsomal preparations from adult Sprague-Dawley rats were examined at 3, 6, 10 and 14 days after intravenous, subcutaneous and intradermal administration of two different strains of Bacillus Calmette-Guérin (BCG). Pasteur liquid strain BCG, injected intravenously at 6 × 10⁸ organisms/m² in normal saline, caused 20-45 per cent reduction of aniline hydroxylase (AH) and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide demethylase (DICD) activities and the cytochrome P-450 content of microsomes from female rats but only 10-25 per cent decrease in these parameters in males. Microsomal protein content was decreased 30-40 per cent in both sexes on days 10-14. Administration of BCG by the subcutaneous route caused only 5-25 per cent impairment of AH and DICD activities in female rats, while intradermal administration of the adjuvant was without discernible effect on the rat hepatic microsomal drug-metabolizing system. The duration of pentobarbital-induced narcosis was increased up to 70 per cent in both male and female rats after intravenous administration of BCG. Tice strain lyophilized BCG at the same dose elicited similar but lesser effects. BCG added in vitro had no effect on AH and DICD activities. Livers of rats treated intravenously contained numerous granulatomous lesions throughout the parenchyma; the damage was variable and less severe in the subcutaneously treated animals. Intradermally treated rats showed normal liver histology.